IEM Flashcards
A 2-month-old infant presents to the clinic with progressive developmental delay, microcephaly, eczema-like rash, and a musty/mousy odor in urine. The parents report that the baby was normal at birth but has been failing to thrive. Laboratory tests reveal increased plasma phenylalanine levels (>20 mg/dL). What is the most likely diagnosis?
A. Phenylketonuria (PKU)
B. Maple Syrup Urine Disease (MSUD)
C. Alkaptonuria
D. Homocystinuria
A. Phenylketonuria (PKU)
π‘ Rationale: PKU is caused by a deficiency of phenylalanine hydroxylase, leading to an accumulation of phenylalanine, which is excreted as phenylketones, giving the urine a musty/mousy odor. Other key findings include intellectual disability, microcephaly, eczematous rash, and growth retardation. Early diagnosis and dietary restriction of phenylalanine can prevent severe neurological damage.
- A newborn with a sweet maple syrup odor
A 5-day-old newborn presents to the ER with poor feeding, lethargy, intermittent apnea, and a distinct burnt sugar/maple syrup odor in urine. Neurological exam reveals hypertonicity with severe muscular rigidity and intermittent opisthotonos. Laboratory studies show elevated plasma levels of leucine, isoleucine, and valine. What is the most appropriate next step?
A. Start a low-protein, branched-chain amino acid-restricted diet
B. Administer high-dose Vitamin B6
C. Start corticosteroids
D. Reassure parents and monitor
A. Start a low-protein, branched-chain amino acid-restricted diet
π‘ Rationale: Maple Syrup Urine Disease (MSUD) is due to deficiency of branched-chain Ξ±-ketoacid dehydrogenase, leading to accumulation of branched-chain amino acids (Leucine, Isoleucine, Valine). This causes neurological deterioration, opisthotonos, and metabolic acidosis. The characteristic maple syrup odor in urine, sweat, and cerumen is a hallmark feature. Management includes dietary restriction of branched-chain amino acids and dialysis in acute cases.
A 3-year-old boy is brought to the clinic by his mother, who noticed that his urine turns black when left standing. He has no complaints of pain, and his development is normal. Physical exam reveals dark pigmentation on the sclera and ear cartilage. What enzyme deficiency is responsible for this condition?
A. Homogentisic acid oxidase
B. Phenylalanine hydroxylase
C. Cystathionine synthase
D. Branched-chain Ξ±-ketoacid dehydrogenase
A. Homogentisic acid oxidase
π‘ Rationale: Alkaptonuria is caused by deficiency of homogentisic acid oxidase, leading to accumulation of homogentisic acid, which turns black when exposed to air. This leads to ochronosis (bluish-black pigmentation of cartilage, sclera, and skin) and early-onset arthritis. Diagnosis is made by urine darkening on standing, and treatment includes nitisinone to reduce homogentisic acid production.
A 2-week-old male newborn presents with persistent vomiting, metabolic acidosis, and a distinct sweaty feet odor in urine. He appears lethargic and has frequent episodes of convulsions. Laboratory findings show severe metabolic acidosis, ketoacidosis, and elevated levels of isovalerylglycine in urine. Which of the following enzyme deficiencies is responsible?
A. Isovaleryl-CoA dehydrogenase
B. Phenylalanine hydroxylase
C. Branched-chain Ξ±-ketoacid dehydrogenase
D. Homogentisic acid oxidase
A. Isovaleryl-CoA dehydrogenase
π‘ Rationale: Isovaleric acidemia is due to deficiency of Isovaleryl-CoA dehydrogenase, leading to accumulation of isovaleric acid, which causes sweaty feet odor in urine, metabolic acidosis, and ketoacidosis. Acute episodes mimic pyloric stenosis with persistent vomiting, lethargy, and convulsions. Diagnosis is confirmed by elevated isovalerylglycine in urine, and treatment includes glycine and carnitine supplementation.
A 4-year-old boy is brought for evaluation due to progressive vision problems. On exam, he has downward lens dislocation (ectopia lentis), long limbs, thin habitus, and a high-arched palate. He also has a history of recurrent thromboembolic episodes. Lab studies show elevated methionine and homocysteine levels. What is the most appropriate treatment?
A. High-dose Vitamin B6 (pyridoxine)
B. Low-phenylalanine diet
C. Low-branched chain amino acid diet
D. Vitamin C supplementation
A. High-dose Vitamin B6 (pyridoxine)
π‘ Rationale: Homocystinuria is due to deficiency of cystathionine synthase, leading to elevated homocysteine and methionine levels. It presents with Marfanoid habitus (tall, thin, long limbs, high-arched palate), ectopia lentis (downward lens dislocation), and recurrent thrombosis. Treatment includes high-dose Vitamin B6, restriction of methionine, and folate/B12 supplementation to reduce homocysteine levels.
A 2-month-old infant presents with progressive developmental delay, microcephaly, a musty/mousy odor in urine, and an eczema-like rash. Parents report that the baby was normal at birth but has been failing to thrive. Laboratory results reveal elevated phenylalanine (>20 mg/dL) with normal tyrosine levels. What is the best next step in management?
A. Dietary restriction of phenylalanine
B. Vitamin B6 supplementation
C. Low-branched chain amino acid diet
D. High-protein diet
A. Dietary restriction of phenylalanine
π‘ Rationale: Phenylketonuria (PKU) is caused by a deficiency of phenylalanine hydroxylase, leading to an accumulation of phenylalanine, which is excreted as phenylketones, causing the musty odor in urine. Other findings include intellectual disability, microcephaly, eczematous rash, and growth retardation.
π Diagnosis: β Phenylalanine (>20 mg/dL), normal tyrosine
π Treatment: Strict dietary restriction of phenylalanine (special formula) to prevent CNS damage.
A 5-year-old boy presents with progressive vision problems, downward lens dislocation, and a history of recurrent deep vein thrombosis. On exam, he has long limbs, arachnodactyly, and a high-arched palate. His mother notes that he has had developmental delays. Lab studies show elevated methionine and homocysteine levels. What is the most appropriate treatment?
A. High-dose Vitamin B6 (pyridoxine)
B. Low-phenylalanine diet
C. Low-branched chain amino acid diet
D. Vitamin C supplementation
A. High-dose Vitamin B6 (pyridoxine)
π‘ Rationale: Homocystinuria is due to a deficiency of cystathionine synthase, leading to elevated homocysteine and methionine levels. It presents with Marfanoid habitus (tall, thin, long limbs, high-arched palate), ectopia lentis (downward lens dislocation), and recurrent thrombosis.
π Diagnosis: β Methionine & homocysteine
π Treatment: High-dose Vitamin B6, methionine restriction, and folate/B12 supplementation to lower homocysteine.
A 7-day-old male is brought to the ER with poor feeding, lethargy, and intermittent apnea. The parents report a distinct maple syrup/burnt sugar odor from his urine. Neurological exam reveals muscular rigidity, opisthotonos, and intermittent convulsions. Blood tests show elevated plasma levels of leucine, isoleucine, and valine. What is the underlying enzyme deficiency?
A. Branched-chain Ξ±-ketoacid dehydrogenase
B. Phenylalanine hydroxylase
C. Cystathionine synthase
D. Isovaleryl-CoA dehydrogenase
A. Branched-chain Ξ±-ketoacid dehydrogenase
π‘ Rationale: Maple Syrup Urine Disease (MSUD) is due to a deficiency of branched-chain Ξ±-ketoacid dehydrogenase, leading to accumulation of branched-chain amino acids (Leucine, Isoleucine, Valine). This causes neurological deterioration, opisthotonos, and metabolic acidosis.
π Diagnosis: β Leucine, Isoleucine, Valine in plasma
π Treatment: Dietary restriction of branched-chain amino acids, peritoneal/hemodialysis in acute cases.
A 2-week-old male newborn presents with persistent vomiting, metabolic acidosis, and a distinct βsweaty feetβ odor in urine. He appears lethargic and has frequent episodes of convulsions. Laboratory findings show severe metabolic acidosis, ketoacidosis, and elevated levels of isovalerylglycine in urine. Which of the following is the best initial treatment?
A. Administration of glycine and L-carnitine
B. Phenylalanine-free diet
C. Branched-chain amino acid-restricted diet
D. Vitamin B6 supplementation
A. Administration of glycine and L-carnitine
π‘ Rationale: Isovaleric Acidemia is caused by a deficiency of Isovaleryl-CoA dehydrogenase, leading to an accumulation of isovaleric acid, which causes a sweaty feet odor in urine, metabolic acidosis, and ketoacidosis.
π Diagnosis: β Isovalerylglycine in urine
π Treatment:
Glycine and L-carnitine supplementation (enhances isovalerylglycine formation and removal).
Dialysis if severe metabolic crisis.
A newborn presents with progressive lethargy, hypotonia, apnea, and poor feeding. The baby is diagnosed with nonketotic hyperglycinemia (NKH) after a metabolic workup. Which of the following enzyme deficiencies is most likely responsible for this condition?
A. Phenylalanine hydroxylase
B. Branched-chain Ξ±-ketoacid dehydrogenase
C. Glycine cleavage enzyme
D. Homogentisic acid oxidase
C. Glycine cleavage enzyme
π‘ Rationale: Nonketotic hyperglycinemia (NKH) is due to a deficiency of the glycine cleavage enzyme system, leading to elevated glycine levels in plasma and CSF. This causes neurological deterioration, seizures, apnea, and hypotonia in neonates. Unlike ketotic hyperglycinemia, there is no ketosis in NKH.
π Diagnosis: Elevated glycine in plasma & CSF
π Treatment: Supportive care; difficult to treat due to inability to remove glycine from the body.
A 3-year-old boy is brought to the clinic after his mother noticed that his urine turns black when left standing. On examination, he has bluish-black pigmentation on his sclera and ear cartilage. What is the most likely metabolic defect?
A. Phenylalanine hydroxylase deficiency
B. Homogentisic acid oxidase deficiency
C. Cystathionine synthase deficiency
D. Branched-chain Ξ±-ketoacid dehydrogenase deficiency
B. Homogentisic acid oxidase deficiency
π‘ Rationale: Alkaptonuria is due to a deficiency of homogentisic acid oxidase, causing an accumulation of homogentisic acid, which oxidizes in urine to turn black when exposed to air. Other features include ochronosis (dark pigmentation in connective tissues like cartilage and sclera) and early-onset arthritis.
π Diagnosis: Black urine on standing, ochronosis
π Treatment: Nitisinone, low-protein diet
A newborn presents with poor feeding, lethargy, vomiting, and seizures. On examination, the baby has tachypnea and a bulging fontanel. Blood tests reveal elevated ammonia levels (>400 ΞΌM). What is the most likely underlying enzyme deficiency?
A. Ornithine transcarbamylase (OTC)
B. Phenylalanine hydroxylase
C. Branched-chain Ξ±-ketoacid dehydrogenase
D. Homogentisic acid oxidase
A. Ornithine transcarbamylase (OTC)
π‘ Rationale: Hyperammonemia in neonates is most commonly due to urea cycle enzyme deficiencies, particularly ornithine transcarbamylase deficiency. It leads to ammonia accumulation, causing neurological symptoms, increased intracranial pressure (bulging fontanel), and metabolic alkalosis.
π Diagnosis: β Ammonia (>400 ΞΌM), normal pH & bicarbonate
π Treatment: Arginine, sodium benzoate, lactulose, dialysis if severe
A 7-year-old girl presents with intermittent vomiting, confusion, and irritability. Her mother notes that these symptoms appear after protein-rich meals. Lab results reveal elevated serum ammonia levels. Which of the following best describes the pathophysiology?
A. Accumulation of homogentisic acid
B. Failure to metabolize glycine
C. Deficiency of urea cycle enzymes
D. Impaired degradation of branched-chain amino acids
C. Deficiency of urea cycle enzymes
π‘ Rationale: Late-onset hyperammonemia can present in older children with intermittent symptoms after high-protein meals due to urea cycle enzyme deficiencies (e.g., OTC deficiency). Accumulated ammonia causes neurological symptoms such as confusion, vomiting, and agitation.
π Diagnosis: β Ammonia, normal glucose & ketones
π Treatment: Protein restriction, ammonia-lowering agents (sodium benzoate, phenylacetate), dialysis in severe cases
A 5-day-old newborn presents with persistent jaundice, poor feeding, vomiting, hepatomegaly, and failure to thrive. On examination, the infant has cataracts. A urine reducing substance test is positive. Which of the following enzyme deficiencies is the most likely cause?
A. Galactose-1-phosphate uridyltransferase (GALT)
B. Glucose-6-phosphatase
C. Ξ±-glucosidase (acid maltase)
D. Lysosomal debranching enzyme
A. Galactose-1-phosphate uridyltransferase (GALT)
π‘ Rationale: Galactosemia is caused by GALT deficiency, leading to accumulation of galactose and its toxic metabolites. It presents in neonates with jaundice, hepatomegaly, vomiting, cataracts, hypoglycemia, and an increased risk of E. coli sepsis.
π Diagnosis: (+) Urine reducing substances (Clinitest)
π Treatment: Strict lactose-free diet (eliminate galactose & lactose) to prevent complications.
A 7-day-old baby is admitted with vomiting, lethargy, jaundice, and hypoglycemia. Physical examination reveals hepatomegaly, and the baby develops E. coli sepsis. Laboratory results show elevated galactose in urine. What dietary modification should be made immediately?
A. Eliminate lactose-containing foods
B. High-protein diet
C. Frequent glucose-rich meals
D. Increase branched-chain amino acid intake
A. Eliminate lactose-containing foods
π‘ Rationale: Classic Galactosemia presents with hypoglycemia, hepatomegaly, cataracts, and an increased risk of neonatal E. coli sepsis due to toxic accumulation of galactose-1-phosphate. Immediate treatment involves removing lactose (found in breast milk and formula) to prevent liver and kidney failure.
π Diagnosis: Urine reducing substances (+) for galactose
π Treatment: Lactose-free diet (soy-based formula)
A 2-year-old boy presents with severe fasting hypoglycemia, hepatomegaly, and lactic acidosis. His parents report that he becomes weak and lethargic when he skips meals. Lab findings reveal elevated lactate and triglycerides. A likely enzyme deficiency is:
A. Glucose-6-phosphatase
B. Glycogen phosphorylase
C. Lysosomal Ξ±-glucosidase
D. Acid maltase
A. Glucose-6-phosphatase
π‘ Rationale: Von Gierke Disease (GSD Type I) is caused by a glucose-6-phosphatase deficiency, leading to severe fasting hypoglycemia, hepatomegaly, lactic acidosis, hyperuricemia, and hyperlipidemia. These children rely on frequent glucose intake to prevent hypoglycemia.
π Diagnosis: Elevated lactate, uric acid, and lipids
π Treatment: Frequent cornstarch/glucose feeds, avoid fasting
A 6-month-old boy is brought in for progressive muscle weakness, poor feeding, and respiratory difficulty. He has macroglossia, hypotonia, and cardiomegaly. A muscle biopsy reveals lysosomal glycogen accumulation. What is the most likely diagnosis?
A. Pompe Disease (GSD Type II)
B. McArdle Disease (GSD Type V)
C. Von Gierke Disease (GSD Type I)
D. Cori Disease (GSD Type III)
A. Pompe Disease (GSD Type II)
π‘ Rationale: Pompe Disease (GSD Type II) is caused by deficiency of lysosomal acid Ξ±-glucosidase, leading to accumulation of glycogen in lysosomes, primarily affecting heart and skeletal muscle. It presents with floppy baby syndrome, cardiomegaly, and respiratory failure.
π Diagnosis: Lysosomal glycogen accumulation on muscle biopsy
π Treatment: Enzyme replacement therapy (ERT) with recombinant Ξ±-glucosidase
A 10-year-old boy complains of muscle cramps, exercise intolerance, and dark-colored urine after intense exercise. He reports that he cannot keep up with his peers during physical activity. Which enzyme is deficient?
A. Myophosphorylase (muscle glycogen phosphorylase)
B. Lysosomal Ξ±-glucosidase
C. Glycogen debranching enzyme
D. Glucose-6-phosphatase
A. Myophosphorylase (muscle glycogen phosphorylase)
π‘ Rationale: McArdle Disease (GSD Type V) is caused by a deficiency of muscle glycogen phosphorylase, leading to impaired glycogen breakdown in muscles. It presents with exercise-induced muscle cramps, myoglobinuria (dark urine), and second-wind phenomenon (improved endurance after rest).
π Diagnosis: Increased creatine kinase (CK), no lactate rise after exercise
π Treatment: Avoid intense exercise, high-protein diet
A 2-year-old boy presents with progressive developmental delay, coarse facial features, hepatosplenomegaly, and skeletal deformities. His mother notes that he has had recurrent ear infections and noisy breathing. On examination, he has corneal clouding and short stature. Which of the following enzyme deficiencies is most likely responsible?
A. Iduronate-2-sulfatase
B. Ξ±-L-iduronidase
C. Glucose-6-phosphatase
D. Lysosomal Ξ±-glucosidase
B. Ξ±-L-iduronidase
π‘ Rationale: Hurler Syndrome (MPS I-H) is caused by a deficiency of Ξ±-L-iduronidase, leading to accumulation of dermatan sulfate and heparan sulfate. It presents with coarse facial features, corneal clouding, hepatosplenomegaly, skeletal deformities (dysostosis multiplex), developmental delay, and recurrent infections.
π Diagnosis: Elevated mucopolysaccharides in urine
π Treatment: Enzyme replacement therapy (ERT), supportive care
A 5-year-old boy presents with progressive skeletal deformities, short stature, joint stiffness, and hearing loss. His parents note that his intelligence is normal. Physical exam reveals coarse facial features, hepatosplenomegaly, and valvular heart disease. He does not have corneal clouding. What is the most likely diagnosis?
A. Hurler Syndrome (MPS I-H)
B. Hunter Syndrome (MPS II)
C. Sanfilippo Syndrome (MPS III)
D. Morquio Syndrome (MPS IV)
B. Hunter Syndrome (MPS II)
π‘ Rationale: Hunter Syndrome (MPS II) is an X-linked recessive disorder caused by a deficiency of iduronate-2-sulfatase. It presents with coarse facial features, short stature, joint stiffness, hepatosplenomegaly, and progressive skeletal deformities, but WITHOUT corneal clouding (unlike Hurler Syndrome).
π Diagnosis: Elevated dermatan & heparan sulfate in urine
π Treatment: Enzyme replacement therapy (Idursulfase), supportive care
A 3-year-old boy presents with delayed milestones, progressive developmental regression, recurrent ear infections, and noisy breathing. Physical exam reveals coarse facial features, hepatosplenomegaly, and corneal clouding. Which of the following complications is the most likely cause of death in this patient?
A. Congestive heart failure due to valvular disease
B. Acute liver failure
C. Renal failure
D. Intracranial hemorrhage
A. Congestive heart failure due to valvular disease
π‘ Rationale: Hurler Syndrome (MPS I-H) is a progressive disorder that leads to cardiac complications, including valvular heart disease and coronary artery narrowing, which can cause congestive heart failure.
π Diagnosis: Corneal clouding + Developmental regression + Hepatosplenomegaly
π Treatment: Bone marrow transplant & enzyme replacement therapy (ERT)
A 6-year-old boy presents with progressive joint stiffness, short stature, and hepatosplenomegaly. His teacher reports that he is performing well academically, but his mobility is declining due to contractures. He does not have corneal clouding. What is the inheritance pattern of his disease?
A. Autosomal dominant
B. Autosomal recessive
C. X-linked recessive
D. Mitochondrial inheritance
C. X-linked recessive
π‘ Rationale: Hunter Syndrome (MPS II) is the only mucopolysaccharidosis that is X-linked recessive, meaning it almost exclusively affects males. Unlike Hurler Syndrome, Hunter Syndrome does NOT cause corneal clouding and has milder cognitive involvement.
π Diagnosis: Joint stiffness + Short stature + No corneal clouding
π Treatment: Enzyme replacement therapy (Idursulfase), supportive care
A 2-year-old boy presents with coarse facial features, skeletal deformities, hepatosplenomegaly, and corneal clouding. His parents report recurrent respiratory infections and noisy breathing. Radiographs show dysostosis multiplex. What is the biochemical abnormality responsible for this condition?
A. Accumulation of glycosaminoglycans (GAGs)
B. Accumulation of glycogen in lysosomes
C. Defective fatty acid oxidation
D. Inability to metabolize branched-chain amino acids
A. Accumulation of glycosaminoglycans (GAGs)
π‘ Rationale: Hurler Syndrome (MPS I-H) results from a deficiency of Ξ±-L-iduronidase, leading to accumulation of dermatan sulfate and heparan sulfate (types of glycosaminoglycans). This causes coarse facial features, hepatosplenomegaly, corneal clouding, and skeletal deformities (dysostosis multiplex).
π Diagnosis: β GAGs in urine
π Treatment: Bone marrow transplant & enzyme replacement therapy
A 5-year-old boy presents with progressive hepatosplenomegaly, bone pain, easy bruising, and fatigue. Physical examination reveals pallor, a distended abdomen, and mild thrombocytopenia. A bone marrow biopsy shows lipid-laden macrophages with a crumpled tissue paper appearance. What is the most likely diagnosis?
A. Gaucherβs Disease
B. Niemann-Pick Disease
C. Tay-Sachs Disease
D. Fabry Disease
A. Gaucherβs Disease
π‘ Rationale: Gaucherβs Disease is caused by a deficiency of Ξ²-glucosidase (glucocerebrosidase), leading to the accumulation of glucocerebroside in macrophages. This results in hepatosplenomegaly, pancytopenia, bone pain, and osteonecrosis. The hallmark finding is Gaucher cells (lipid-laden macrophages with a crumpled tissue paper appearance).
π Diagnosis: Bone marrow biopsy (Gaucher cells), enzyme assay
π Treatment: Enzyme replacement therapy (Imiglucerase), supportive care
A 4-month-old baby presents with progressive neurodegeneration, hypotonia, and hepatosplenomegaly. His parents note that he has feeding difficulties and has lost previously acquired motor skills. On ophthalmologic exam, he has a cherry-red macula. What is the most likely diagnosis?
A. Gaucherβs Disease
B. Niemann-Pick Disease
C. Tay-Sachs Disease
D. Krabbe Disease
B. Niemann-Pick Disease
π‘ Rationale: Niemann-Pick Disease is caused by sphingomyelinase deficiency, leading to accumulation of sphingomyelin in macrophages (foam cells). It presents with hepatosplenomegaly, progressive neurodegeneration, hypotonia, and a cherry-red macula. Unlike Tay-Sachs, Niemann-Pick has hepatosplenomegaly.
π Diagnosis: Foam cells on bone marrow biopsy, enzyme assay
π Treatment: No cure; supportive care
A 6-month-old girl is brought in for evaluation due to progressive weakness, loss of motor milestones, exaggerated startle response, and poor feeding. Ophthalmologic exam reveals a cherry-red macula, but there is no hepatosplenomegaly. What is the most likely enzyme deficiency?
A. Glucocerebrosidase (Ξ²-glucosidase)
B. Sphingomyelinase
C. Hexosaminidase A
D. Galactocerebrosidase
C. Hexosaminidase A
π‘ Rationale: Tay-Sachs Disease is due to a deficiency of Hexosaminidase A, leading to the accumulation of GM2 gangliosides in neurons. It presents with progressive neurodegeneration, hyperreflexia, an exaggerated startle response, and a cherry-red macula. Unlike Niemann-Pick Disease, there is NO hepatosplenomegaly in Tay-Sachs.
π Diagnosis: Enzyme assay (β Hexosaminidase A), cherry-red macula
π Treatment: Supportive care; no cure
A 3-year-old child presents with hepatosplenomegaly, ataxia, and developmental regression. His mother states that he was previously developing normally but has now lost the ability to walk. A bone marrow biopsy reveals foam cells. Which of the following conditions is most likely?
A. Gaucherβs Disease
B. Niemann-Pick Disease
C. Tay-Sachs Disease
D. Fabry Disease
B. Niemann-Pick Disease
π‘ Rationale: Niemann-Pick Disease (Type A and B) presents with progressive neurodegeneration, hepatosplenomegaly, ataxia, and developmental regression due to sphingomyelin accumulation. The hallmark histologic feature is foam cells in the bone marrow.
π Diagnosis: Foam cells on bone marrow biopsy, enzyme assay
π Treatment: Supportive care; no cure
A 10-year-old boy presents with episodes of bone pain, easy bruising, hepatosplenomegaly, and fatigue. X-rays reveal osteonecrosis of the femur, and blood tests show pancytopenia. A bone marrow biopsy reveals lipid-laden macrophages with a crumpled tissue paper appearance. What is the best treatment for this condition?
A. High-dose corticosteroids
B. Enzyme replacement therapy (ERT)
C. Bone marrow transplant
D. Low-fat diet
B. Enzyme replacement therapy (ERT)
π‘ Rationale: Gaucherβs Disease is due to Ξ²-glucosidase deficiency, leading to glucocerebroside accumulation in macrophages. It presents with bone crises, hepatosplenomegaly, and pancytopenia. ERT (Imiglucerase) is the first-line treatment.
π Diagnosis: Bone marrow biopsy (Gaucher cells)
π Treatment: ERT (Imiglucerase), supportive care
A 2-year-old boy presents with delayed motor milestones, self-mutilating behavior (lip & finger biting), spasticity, and recurrent vomiting. Laboratory findings show hyperuricemia. His mother notes that he has had orange sand-like deposits in his diaper. What is the most likely diagnosis?
A. Adenosine deaminase deficiency
B. Lesch-Nyhan Syndrome
C. Ornithine transcarbamylase deficiency
D. Glucose-6-phosphatase deficiency
B. Lesch-Nyhan Syndrome
π‘ Rationale: Lesch-Nyhan Syndrome is an X-linked recessive disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT). It leads to excess uric acid production, resulting in self-mutilation, hyperuricemia, gout-like symptoms, and neurologic dysfunction (spasticity, dystonia).
π Diagnosis: β Uric acid, orange sand-like urate crystals in diapers
π Treatment: Allopurinol (reduces uric acid), supportive therapy
A 6-year-old boy presents with growth failure, loss of subcutaneous fat, joint stiffness, alopecia, and a beaked nose. His mother reports that he has aged rapidly over the past few years. On examination, he has prominent scalp veins, thin skin, and sclerotic nails. What is the most likely diagnosis?
A. Werner Syndrome
B. Hutchinson-Gilford Progeria Syndrome
C. Marfan Syndrome
D. Cockayne Syndrome
B. Hutchinson-Gilford Progeria Syndrome
π‘ Rationale: Progeria (Hutchinson-Gilford Progeria Syndrome) is caused by a mutation in the LMNA gene, leading to premature aging, growth failure, alopecia, loss of subcutaneous fat, and joint stiffness. Cardiovascular disease (atherosclerosis) is a major cause of death.
π Diagnosis: LMNA gene mutation
π Treatment: Supportive care, management of cardiovascular complications
A 16-year-old girl presents with recurrent episodes of severe abdominal pain, confusion, hallucinations, and peripheral neuropathy. She reports that these symptoms worsen after alcohol consumption and fasting. Physical examination reveals tachycardia and autonomic instability. What is the most likely diagnosis?
A. Acute Intermittent Porphyria (AIP)
B. Lead poisoning
C. Phenylketonuria
D. Hyperammonemia
A. Acute Intermittent Porphyria (AIP)
π‘ Rationale: Porphyria is due to defective heme biosynthesis, leading to neurovisceral symptoms (abdominal pain, hallucinations, neuropathy, tachycardia). Symptoms worsen with alcohol, fasting, and medications (e.g., barbiturates).
π Diagnosis: β Porphyrins in urine (reddish urine)
π Treatment: Glucose loading, IV heme therapy (to suppress heme synthesis)
- A neonate with recurrent hypoglycemia and hepatomegaly
A newborn presents with lethargy, seizures, and recurrent episodes of hypoglycemia. On examination, he has hepatomegaly. Lab results show hypoglycemia with elevated ketones. What is the most likely enzyme deficiency?
A. Glucose-6-phosphatase
B. Ornithine transcarbamylase
C. Acid maltase
D. Lysosomal hydrolase
A. Glucose-6-phosphatase
π‘ Rationale: Glucose-6-phosphatase deficiency (Von Gierke Disease, GSD I) leads to severe fasting hypoglycemia, hepatomegaly, and lactic acidosis. Ketotic hypoglycemia is a hallmark finding.
π Diagnosis: Hypoglycemia with ketosis, elevated lactate
π Treatment: Frequent glucose/cornstarch feeds, avoid fasting
A 2-year-old girl presents with episodes of hypoglycemia, seizures, and irritability after prolonged fasting. Labs show low blood glucose, elevated free fatty acids, and no ketones. What is the most likely metabolic defect?
A. Fatty Acid Oxidation Disorder (MCAD deficiency)
B. Glycogen storage disease
C. Insulinoma
D. Galactosemia
A. Fatty Acid Oxidation Disorder (MCAD deficiency)
π‘ Rationale: MCAD deficiency (Medium-Chain Acyl-CoA Dehydrogenase Deficiency) leads to fasting hypoglycemia with no ketone production due to impaired fatty acid breakdown. It presents with seizures, irritability, and lethargy after fasting.
π Diagnosis: Hypoglycemia + NO ketones, β Free fatty acids
π Treatment: Avoid fasting, frequent carbohydrate meals
