2025 – PAGE 360 – INBORN ERRORS OF METABOLISM & MISCELLANEOUS METABOLIC DISORDERS

INFANT OF A DIABETIC MOTHER (IDM)

Infants of diabetic mothers (IDM) will have CARDIAC, CARDIAC, CARDIAC, and NEURAL TUBE DEFECTS! Patients are especially prone to having septal defects. They may also have coarctation of the aorta, hypertrophic obstructive cardiomyopathy (HOCM), truncus arteriosus, dextrocardia, and more. Can also have rib or vertebral column abnormalities, hydrocephalus, macrosomia/LGA size (with birth trauma), small Left colon, duodenal atresia (“double bubble” or “gaseous distention in both the stomach and duodenum”), apnea, hypOcalcemia, hypOmagnesemia, hypOphosphatemia, hyperbilirubinemia, polycythemia, vascular thromboses and RDS (look for tachypnea).

• PEARL: The hypoglycemia may not occur until ONE or TWO days after birth.
• PEARL: For hypocalcemia, look for jitteriness, a prolonged QT, Chvostek’s sign (tapping the facial nerve elicits a twitch), or Trousseau’s sign (carpopedal spasm noted when the wrist is clasped).

PURINE AND PYRIMIDINE DISORDERS

Purine and pyrimidine disorders may cause recurrent infections, developmental delay/cognitive defects, and failure to thrive (FTT).

• LESCH-NYHANSYNDROME: Look for SELF MUTILATION + choreiform movements + intellectual disability + elevated uric acid levels (can also get gout). This is X-linked.
  • MNEMONIC: LeX Luthor in the Superman series was a little crazy. Call it “leX-nyhan” to remember that it’s X-linked and to consider it in male patients.
  • MNEMONIC: Rename it “LET’S EAT MY HAND (lesch-nyhan) syndrome because it won’t stop DANCIN’!” Dancin’ = Choreiform movements.
• ADENOSINEDEAMINASE (ADA) DEFICIENCY: ADA deficiency is a rare disorder in which the lack of ADA causes toxic build ups which hamper the ability of highly mitotically active cells, such as T cells and B cells. ADA deficiency is responsible for about 15% of Severe Combined Immunodeficiency Syndrome (SCID) cases. Look for recurrent infections and developmental delay/cognitive defects.

(DOUBLE TAKE) WILSON’S DISEASE

Wilson Disease (AKA Wilson’s Disease) is an autosomal recessive disorder resulting in excess copper accumulation, especially within the liver and brain. Accumulation in the liver can lead to hepatomegaly, spider nevi, esophageal varices, and a Coombs-negative hemolytic anemia. Accumulation in the brain can lead to neurologic changes including tremors, poor school performance, ataxia, abnormal eye movements, and spasms. On eye exam, a Kayser-Fleischer ring may be visible. Copper levels are low in the serum but high in the tissues. Diagnose by LIVER BIOPSY. Treat with PENICILLAMINE, a copper chelator.

PEARLS: Diagnose by LIVER BIOPSY. Abnormal eye movements and a Fleischer ring may be present, but there is no visual disturbance. Kayser-Fleischer rings are seen in 90% of symptomatic patients, and almost 100% of patients with neurologic manifestations. Screen family members with CERULOPLASMIN levels. Ceruloplasmin is made in the liver and is the primary copper-carrying protein. If the level is LOW, that suggests Wilson’s Disease because excess copper is not being incorporated into ceruloplasmin, and is therefore still in the TISSUES. Therefore, supportive labs may include a low serum ceruloplasmin, high tissue copper levels, high urine copper levels and low serum copper levels.

IMAGE: www.pbrlinks.com/WILSONS1
IMAGE: www.pbrlinks.com/WILSONS2

MNEMONICS: Treat with a “COPPER PENNY-cillamine.” Also, ever heard of Wilsons, the leather company that makes baseball gloves? See the image below to note the strong resemblance in color to a COPPER PENNY. This should help you remember that Wilsons Disease has to do with copper, and that it is treated with “PENNY-cillamine.”