Maple syrup urine disease and oculocutaneous albinism in twins.

Sir,

Maple syrup urine disease (MSUD) is an inborn error of metabolism (IEM) characterized by a defect in the catabolic pathway of branched-chain amino acids resulting from a deficiency of branched-chain α-ketoacid dehydrogenase. Classic MSUD presents with life-threatening clinical manifestations in the neonatal period.[1] Twins, in the newborn period, presented to the neonatal intensive care unit (ICU) with unexplained encephalopathy and abnormal urine odor with one twin manifesting oculocutaneous albinism. They were both diagnosed as having MSUD. MSUD is inherited in an autosomal recessive fashion and occurs in 1 in 200,000 individuals.[2] Oculocutaneous albinism has a prevalence of 1/40,000.[3] It has an autosomal recessive inheritance pattern and is a disorder of melanin biosynthesis. MSUD in monozygotic twins has been reported in the literature.[4] However, there has been no report on the occurrence of MSUD and oculocutaneous albinism in a single individual so far.

Twins, males, born to a healthy mother were extracted by elective cesarean section with birth weights of 2.3 kg and 2 kg [Figure 1]. Both cried immediately after birth and were started on direct breastfeeds soon after birth. The first twin presented to the neonatal ICU on the 6th day of life with lethargy, refusal of feeds and hurried breathing. Hypopigmented skin, hair and iris were also noted, which is diagnostic of oculocutaneous albinism. The second twin was admitted a day later with similar complaints, but did not have any hypopigmentation. The parents had a second degree consanguineous marriage with history of albinism in the maternal grand-mother, and neonatal deaths and miscarriages in the extended family. On examination, abnormal urine odor, similar to that of burnt sugar, was noted in both the babies. Both had a weight loss exceeding 500 g in the 1st week of life. Tachypnea, gross hypotonia and poor reflexes were observed in both siblings.

Figure 1

Picture of twins with the one on the left having oculocutaneous albinism

Severe hypoglycemia was present in both neonates at admission. Despite dextrose infusion and other supportive management, the condition of both neonates deteriorated further, with refractory hypoglycemia. Lab results revealed metabolic acidosis with increased anion gap. Sepsis screen in both were negative. Urine analysis revealed presence of ketone bodies and did not have any reducing substances. Elevated ammonia levels and lactic acidosis observed helped to narrow down the differential diagnosis to organic acidemia. Tandem mass spectrometry revealed elevated leucine, isoleucine and valine in the twins, confirming the diagnosis of MSUD. The neonates were treated with thiamine, carnitine, vitamin cocktail, dextrose infusion and supportive management.

Unexplained encephalopathy, high anion gap metabolic acidosis, severe hypoglycemia, abnormal urine odor and a negative sepsis screen are pointers for IEM in neonatal period. The presence of hyperammonemia, lactic acidosis, ketonuria with hypoglycemia is unique to organic acidemias. Though rare, IEM is a condition seen periodically in clinical practice. Timely diagnosis and appropriate management can lead to better quality of life with decreased morbidities in affected children.