Bio chem Enz contd 8-3 Flashcards
This patient’s mild intellectual disability, combined with the cutaneous findings, previous MRI results, and history of having a rhabdomyoma that regressed when she was younger are indicative of ?
tuberous sclerosis, an autosomal dominant disorder affecting tuberin and hamartin proteins, which regulate cellular growth and differentiation. Two gene loci for tuberous sclerosis have been identified on chromosomes 9 and 16. Tuberous sclerosis has a variety of manifestations: Subependymal brain tubers Seizures Intellectual disability Renal angiomyolipomas Cardiac rhabdomyomas Astrocytomas Pulmonary lymphangioleiomyomatosis Cutaneous manifestations: hypopigmented ash-leaf spot, shagreen patch, and facial angiofibromas
Neurofibromatosis 2 (NF-2) is an autosomal dominant disorder caused by mutations in the NF2 gene on chromosome 22. NF2 causes bilateral acoustic neuromas as a characteristic finding, which may manifest with bilateral tinnitus and hearing loss. Leber hereditary optic neuropathy is due to a ?
mitochondrial mutation that causes degeneration of the optic nerve with rapid loss of central vision, leading to a permanent central scotoma.
von Hippel-Lindau syndrome is an autosomal dominant disorder characterized by abnormal blood vessel growth. The overgrowth of blood vessels leads to angiomas and hemangioblastomas in the retina, brain, and spinal cord, as well as in other regions of the body. Untreated retinal hemangiomas can rupture, leading to retinal detachment.
Glaucoma is associated with Sturge-Weber syndrome, which is caused by a mutation in the GNAQ gene.
Tuberous sclerosis is an autosomal dominant disease in which tumors (especially hamartomas) develop in multiple organs. It is characterized by?
ash-leaf spots, shagreen patches, cardiac rhabdomyomas, renal angiomyolipomas, and epilepsy.
This patient with intellectual disability presents with painful, swollen joints and uncontrolled spastic movements. He also has a history of muscular hypotonia. He is most likely suffering from Lesch-Nyhan syndrome, an X-linked recessive disorder caused by?
a deficiency in hypoxanthine guanine phosphoribosyltransferase (HGPRT).
SCID, a deficiency of adenosine deaminase, would present with repeated infections of fungal, viral, and bacterial origin early in life.
Gaucher disease is a deficiency of glucocerebrosidase, presenting with anemia, thrombocytopenia, and vertebral issues.
A mutation of an enzyme in ?
the de novo purine biosynthetic pathway would result in anemia findings such as megaloblastosis.
Xeroderma pigmentosum, a DNA excision repair enzyme deficiency would result in sensitivity to sunlight and radiation.
Lesch-Nyhan syndrome is an X-linked recessive disorder caused by ?
a deficiency in hypoxanthine-guanine phosphoribosyltransferase, an enzyme in the purine salvage pathway. It results in an accumulation of uric acid and is associated with self-mutilation behaviors, intellectual disability, gout, and movement disorders.
This child has multiple congenital birth defects that are consistent with Patau syndrome, a rare autosomal trisomy characterized by holoProsencephaly, cleft liP/Palate, microphthalmia (small eyes), severe intellectual disability, Polydactyly (extra digits), congenital heart disease, cutis aPlasia (localized absence of skin at birth), and rocker-bottom feet. It is caused by?
trisomy 13.
Trisomy 18 (Edward syndrome) carries a similar prognosis. It shares the rocker-bottom feet, congenital heart defects, and severe intellectual disability of trisomy 13. However, it is distinguished by micrognathia (small jaw), low-set ears, and clenched fists with overlapping digits.
Trisomy 21 (Down syndrome) is the most common viable chromosomal disorder. Accordingly, birth defects associated with trisomy 21 are?
less severe, including flat facies, prominent epicanthal folds, single palmar crease, and hypotonia.
Deletion of 5p is associated with cri-du-chat syndrome, which is more likely to manifest physically with microcephaly, epicanthal folds, and cardiac defects.
Deletion of 11p13 is associated with the WAGR complex, which includes Wilms tumor, aniridia, genitourinary abnormalities, and intellectual disability (historically called mental retardation).
Patau syndrome (trisomy 13) is characterized by holoprosencephaly, cleft lip/palate, microphthalmia, cutis aplasia, intellectual disability, polydactyly, congenital heart disease, and rocker-bottom feet. The First Trimester Screen combines?
the blood tests for PAPP-A and hCG, an ultrasound exam, and screens for trisomy 13, trisomy 18 (Edwards syndrome), and trisomy 21 (Down syndrome).
This young child has significant hepatosplenomegaly and progressive widespread neurodegeneration (as evidenced by his failure to hit developmental milestones). Fundoscopic examination shows a cherry-red spot on the macula (first image). The combination of these symptoms and findings suggest a diagnosis of Niemann-Pick disease.
Niemann-Pick disease is caused by?
the absence of the enzyme sphingomyelinase which converts sphingomyelin to ceramide. The deficiency of sphingomyelinase in patients with Niemann-Pick disease causes accumulation of sphingomyelin and cholesterol in parenchymal and reticuloendothelial cells. Under a light microscopy, these lipid-laden macrophages have a foamy appearance, which is consistent with the findings on the bone marrow biopsy examination. The foamy appearance is caused by the presence of innumerable small vacuoles of relatively uniform size.
Fabry disease is caused by a mutation of a-galactosidase A which converts ceramide trihexoside to lactosyl cerebroside. It manifests in early childhood with peripheral neuropathy, angiokeratomas (tiny painless papules), renal insufficiency and cardiovascular disease (not seen in our patient).
Krabbe disease is caused by a mutation in galactocerebrosidase which converts galactocerebroside to ceramide. Patients with this disease develop optic atrophy (not a cherry-red macula spot), peripheral neuropathy, and developmental delay.
Tay-Sachs disease and Niemann-Pick have a similar clinical presentation of progressive neurological decay with a cherry-red spot on the macula. Tay-Sachs is caused by?
a lack of ß-hexosaminidase A which converts ganglioside M2 to ganglioside M3. The key distinguishing feature is the lack of hepatosplenomegaly in Tay-Sachs disease.
Lastly, Gaucher disease is caused by a lack of ß-glucocerebrosidase which converts glucocerebroside to ceramide. While patients with Gaucher disease may have hepatosplenomegaly, the other symptoms of skeletal weakness, pathologic fractures and bruising (because of thrombocytopenia) are absent in this patient.
At birth, a baby exhibits micrognathia, malformed ears, ocular hypertelorism, syndactyly, and clenched hands, with the fifth finger overriding the fourth finger and the index finger overriding the middle finger. A karyotype shows three copies of chromosome 18.
Which of the following symptoms is also associated with this disorder?
More than 90% of patients with Edwards syndrome have some form of congenital heart malformation, the most common being ventricular septal defect with pulmonary and aortic valve defects. Other types of cardiac malformations can also occur.
Anencephaly is not associated with Edwards syndrome. This condition is associated with abnormal cranial morphology, commonly described as a narrow cranium with a prominent occiput.
Patients with Edwards syndrome show many malformations of the hands and feet, but limb atresia is not characteristic.
Patients with Edwards syndrome have?
pulmonary hypoplasia and abnormal placement of the lungs, not pulmonary hamartomas.
Brushfield spots, which are spots seen on the iris, are associated with Down syndrome (trisomy 21).
Edwards syndrome, or trisomy 18, is characterized by?
flexed fingers with overriding digits, narrow cranium with prominent occiput, and congenital heart anomalies.
This patient had a urinary tract infection and was prescribed a common antibiotic combination. He calls his physician 3 days later and complains of fatigue, darkening urine, and jaundice, which suggest that he is experiencing?
drug-induced hemolysis as a result of glucose-6-phosphate dehydrogenase (G6PD) deficiency. The laboratory test results showing decreases in hemoglobin, red blood cell (RBC) count, and hematocrit support this diagnosis.
