Em metabolic

Question 1

Most patients are diagnosed after the age of 3 years since they are asymptomatic at birth and manifestation may be observed but very non-specific, such as retarded growth and failure to thrive. Older children will have ocular manifestation like astigmatism, glaucoma, cataracts, lens subluxation (ectopia lentis), retinal detachment, and optic atrophy. Mental retardation is also common. They may also show skeletal defects like that seen in Marfan syndrome. Children will have blue eyes, fair skin, and a distinct malar flush. Generalized osteoporosis is seen on x-ray.

Answer 1

Cysthathionine synthase deficiency or Classic Homocystinuria or Homocystinuria type I, which is the most common type of homocystinuria. Diagnosis is made by the presence of homocysteine and methionine in the body fluids. Most individuals respond to high doses of Vitamin B6 because they still have a little enzyme activity.

Question 2

Usually in complete absence of enzymatic activity, _____ is manifested by neonatal apneic episodes and myoclonic seizure that may lead to coma and death. In partial absence, a more chronic clinical picture is seen including mental retardation, microcephaly, seizure, and spasticity.

Answer 2

Methylene tetrahydrofolate deficiency, or Homocystinuria Type III, is an Autosomal recessive disorder that is believed to affect the genes in the short arm of chromosome 1. Megaloblastic Anemia is absent, which makes it different from Type II.

Question 3

_____ is characterized by vomiting, weakness, hypotonia, and the development of megaloblastic anemia, which makes it different from type III and developmental delay during the first few months of life. Diagnosis is made by complementation studies in cultured fibroblast and amniotic cell culture during prenatal screening. Patients respond to Vitamin B12 at 1-2 mg/24 hr.

Answer 3

Methylcobalamin formation defects, or Homocystinuria Type II,

Question 4

_____ is a defect in the biosynthesis and distribution of melanin due to deficiency of tyrosinase, manifested by hypopigmentation of the skin and ocular symptoms such as strabismus, photophobia, and decreased visual acuity. Late and serious complications are also seen such as blindness and skin cancer.

Answer 4

Tyrosinase deficiency, or Albinism,

Question 5

____ is an autosomal recessive sphingolipidosis caused by deficient activity of a lysosomal enzyme, galactocerebrosidase (GALC), leading to destruction of oligodendroglia and the CNS and subsequent demyelination. Typical age on onset is 3-6 months. An infantile onset or classic form follows normal early development and accounts for the vast majority of cases; it is characterized by spasticity, irritability, hypertonia, hyperesthesia, psychomotor arrest, and then rapidly progressive neurologic degeneration, hyperreflexia, optic atrophy, persistent decerebrate posturing, and early death. Feeding difficulties, such as vomiting and reflux, may cause failure to thrive

Answer 5

Krabbe disease. Neither routine blood chemistry tests nor urinalysis reveal any specific abnormalities. CSF reveals elevated protein levels and an abnormal pattern of electrophoresis. Measurement of GALC activity helps confirm the diagnosis. MRI detects high intensity areas of demyelination in the brainstem and cerebellum. Sequelae, including infection and respiratory failure, cause most deaths usually before 2 years of age.

Hematopoietic stem cell or bone marrow transplantation should be considered

Question 6

____ is hepatic porphyria; it presents with neurovisceral manifestions and does not affect the skin. There is a defect in the heme metabolism resulting in excessive production of porphyrins and their precursors. It has an autosomal dominant mode of inheritance. Neurological involvement may also include cortical blindness and peripheral neuropathy.

Answer 6

Acute Intermittent Porphyria. There is deficiency of the enzyme porphobilinogen deaminase, which converts porphobilinogen into hydroxymethylbilane. This leads to accumulation of prophobillinogen and delta-aminolevulinic acid (ALA).

Question 7

Porphyrias are broadly divided into 2 categories:

Answer 7

(1) Hepatic and (2) Erythropoetic depending on the site of accumulation of porphyrins. Hepatic porphyrias present with neurovisceral manifestations. Erythropoetic porphyrias present with cutaneous manifestations.

Question 8

_____ presented with neurovisceral symptoms like abdominal pain, vomiting, constipation, hypertension, and tachycardia. Neurological involvement is manifested as seizures. Skin rash is characteristically absent. The diagnosis is further supported by the fact that urine is red in color and shows increased amounts of porphobilinogen.

Answer 8

acute intermittent porphyria (AIP).

Drugs like phenobarbitone, sulphonamides, progesterone, and alcohol can aggravate an attack of AIP.

Question 9

It can be diagnosed by demonstration of increased urinary porphobilinogen excretion in urine. Imaging studies are not helpful in the diagnosis of AIP.

Answer 9

Treatment goal is to decrease heme synthesis and reduce the production of porphyrin precursors. High doses of glucose 400g/day are useful in treatment of mild attacks. Pain is controlled by narcotics.

Hemin (Panhemetin) 4mg/Kg/day is given intravenously for 4 days. It shuts down production of porphyrins and porphyrin precursors.

Question 10

Erythropoetic porphyrias primarily affect

Answer 10

the skin leading to photosensitivity and blistering lesions of the skin.

Question 11

usually appears for the first time in adults. Erosions and bullae appear on the sun exposed skin over the hands, forearms, face, and feet. It leaves hyperpigmented patches and hypopigmented scars. Urine has a port wine color tint. There is deficiency of uroporphyrinogen (URO) decarboxylase.

Answer 11

porphyria cutanea tarda PCT

Question 12

___ may manifest during neonatal period with photosensitivity. Exposure to sun or phototherapy may cause severe blistering lesions on the exposed areas of the skin of the face and hands. There may be bullae and vesicles leading to scarring and thickness of skin, sometimes causing mutilation. Urine is reddish in color. Pink staining.of diaper may be observed during infancy.

Answer 12

CEP. Enzyme uroporphyrinogen (URO) synthase is deficient.

Question 13

__ is a mixed type of porphyria, i.e. it has cutaneous manifestations like PCT and can also have neurovisceral symptoms, but they occur less frequently than AIP. Enzyme protoporphyrinogen (PROTO) oxidase is deficient. Urinary porphobilinogen and delta- aminolevulinic acid are greatly increased.

Answer 13

VP

Question 14

_____ is a hepatic porphyria. Enzyme coproporphyrinogen (COPRO) oxidase is deficient. It has an autosomal dominant mode of inheritance and is characterized by mild neurovisceral manifestations and cutaneous lesions like PCT.

Answer 14

Hereditary porphyria

Question 15

combination of jaundice, hepatomegaly, hypoglycemia, vomiting, lethargy, feeding difficulties and poor weight gain is typical for classic ______

Answer 15

galactosemia, caused by a deficiency of galactose-1-phosphate uridyl transferase. prevalence of 1 in 40,000 live births, most of the clinical features of the disease are caused by an accumulation of galactose-1-phosphate and toxic derivatives. Galactose as a reducing substance in the urine will not be detected by standard urinalysis methods, which employ glucose oxidase and are specific for glucose. Treatment revolves around eliminating galactose from the diet.

Question 16

classic triad of strabismus, trismus (lockjaw), and opisthotonus in association with spastic and seizure disorder is highly suggestive of the neuronopathic infantile form of On microscopic examination, the cells of the reticuloendothelial system show characteristic wrinkled tissue appearance. Hepatosplenomegaly is another finding suggesting ____

Answer 16

Gaucher’s disease. Gaucher’s disease is caused by the deficiency of glucocerebrosidase and storage of large amounts of glucocerebrosides. Bone marrow biopsy and enzyme analysis can document the biochemical changes and establish the diagnosis. Serum acid phosphatase is characteristically elevated when Gaucher’s disease affects bones but this finding cannot confirm the diagnosis.

Question 17

Diffuse neural involvement leading eventually to cell death and shrinkage of the brain. A cherry red spot is seen in the retina. Lipids accumulate in the retinal ganglion cells making them appear pale thereby accentuating the normal red color to the macular choroid (cherry red spot). The GIT and the respiratory system may also be involved. On histology the affected cells are enlarged and filled with numerous small vacuoles that impart foaminess to the cytoplasm. Frozen section of fresh tissue is positive for fat with Oil red O or Sudan black B.

Answer 17

Niemann-Picks disease is a lysosomal storage disorder. The most common form is associated with deficiency of sphingomyelinase leading to accumulation of sphingomyelin and cholesterol in mononuclear phagocytic and many other cell types eg. ganglion cells. Clinically it manifests soon after birth. Patients usually present with hepatosplenomegaly, failure to thrive, and deterioration of psychomotor function. Survival is limited to 1 to 2yrs. Accumulation of lipids in cells of mononuclear phagocytic system gives rise to massive splenomegaly, enlargement of liver and lymph nodes, and infiltration of bone marrow.

Question 18

Gaucher’s disease is also a lysosomal storage disorder. It is associated with abnormalities in the glucocerebrosidase enzyme with the resultant accumulation of

Answer 18

glucocerebrosides in the mononuclear phagocytic system and in some forms in the CNS.

Question 19

Gaucher’s disease are Type I, which is the most common form. It occurs in adults, and is a chronic non-neuropathic form. It is associated with

Answer 19

massive splenomegaly with resultant pancytopenia or thrombocytopenia, involvement of bone marrow leading to pathological fractures. The life span of the individual is not affected.

Question 20

Some important variants of Type II is an acute neuropathic form. There is associated hepatosplenomegaly and CNS involvement, which presents as convulsions and mental deterioration. Death usually occurs at

Answer 20

a young age. Microscopically in both types the affected cells are known as Gaucher’s cells that are distended with PAS- positive material that has a fibrillary appearance resembling crumpled tissue paper.

Question 21

The child has presented with typical features of metabolic acidosis manifesting with tachypnea, hypoglycemia with altered sensorium, and massive hepatomegaly. The diagnosis is further supported by hyperlipidemia lactic acidosis with a high anion gap and raised uric acid level.

Answer 21

Von Gierke disease or Type I glycogen storage disease (GSD type I).

Question 22

Fabry disease is an X-linked condition caused by deficient alpha-galactosidase A enzyme activity. This results in progressive storage of globotriaosylceramide (GL-3) in cells throughout the body. Classic Fabry disease has onset in childhood/adolescence, and symptoms include acroparasthesias, angiokeratomas, hypohydrosis, corneal and lens opacities that do not affect vision, and proteinuria. With time, ___declines in the 3rd to 5th decade of life and ____ is a major cause of morbidity and mortality.

Answer 22

renal function declines to end-stage renal disease (ESDR).
While there are unusual ocular findings involving the cornea and lens including cornea verticillata and lenticular opacities in Fabry, they do not have blindness. Fabry is associated with depression, anxiety, extreme fatigue, and other psychosocial issues that can adversely affect the quality of life for many affected individuals. However, cognitive deterioration and dementia are not prominent features of this condition. While Fabry disease is a multisystem disorder, the liver does not appear to be adversely affected.