Maple Syrup Urine Disease

Alternative Names

  • MSUD
  • Branched-Chain Ketoaciduria
  • Branched-Chain Alpha-Keto Acid Dehydrogenase Deficiency
  • BCKD Deficiency
  • Keto Acid Decarboxylase Deficiency
  • Maple Syrup Urine Disease, Classic
  • Maple Syrup Urine Disease, Intermediate
  • Maple Syrup Urine Disease, Intermittent
  • Maple Syrup Urine Disease, Thiamine-Responsive
  • Maple Syrup Urine Disease, E3-Deficient, with Lactic Acidosis
  • Maple Syrup Urine Disease, Type Ia
  • MSUD1a
  • Maple Syrup Urine Disease, Type Ib
  • MSUD1b
  • Maple Syrup Urine Disease, Type II
  • MSUD2
  • Maple Syrup Urine Disease, Type III
  • MSUD3
  • Lipoamide Dehydrogenase Deficiency, Lactic Acidosis due to
  • Lactic Acidosis, Congenital Infantile, due to LAD Deficiency
  • Dihydrolipoamide Dehydrogenase Deficiency
  • DLD Deficiency
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Metabolic disorders

OMIM Number

248600

Mode of Inheritance

Autosomal recessive

Gene Map Locus

1p21.2,6q14.1,19q13.2

Description

Maple Syrup Urine Disease (MSUD) is a recessively inherited inborn error of metabolism characterized by the inability to metabolize the branched chain amino acids leucine, isoleucine, and valine, hence, resulting in their accumulation in the blood. The name of the disease derives from the characteristic sweet maple syrupy smell of urine in affected patients. The condition appears in early infancy, where it is characterized by feeding difficulties and avoidance of food, vomiting, seizures, lack of energy, and even coma. If left untreated, the accumulation of the amino acids and their keto acids leads to serious complications, including encephalopathy and progressive neurodegeneration. 

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
248600.G.1JordanUnknown Elevated plasma branched chain amino aci... NM_183050.4:c.490G>AHomozygousAutosomal, RecessiveAl-Jasmi at al. 2016 UAE resident(s) of J...
248600.3Lebanon Ketosis; Lactic acidosis; Abnormal cir... NM_183050.4:c.995C>THomozygousAutosomal, RecessiveNair et al. 2018
248600.6LebanonYes NM_000709.4:c.890G>AHomozygousAutosomal, RecessiveJalkh et al. 2019
248600.1.1LebanonUnknownNoYes Classic maple syrup urine disease... NM_001918.4:c.224G>AHomozygousAutosomal, RecessiveTabbouche et al, 2014
248600.1.2LebanonUnknownNoYes Classic maple syrup urine disease... NM_001918.4:c.224G>AHomozygousAutosomal, RecessiveTabbouche et al, 2014
248600.1.3LebanonUnknownNoYes Intermediate maple syrup urine disease... NM_001918.4:c.1430T>GHomozygousAutosomal, RecessiveTabbouche et al, 2014
248600.1.4LebanonUnknownNoYes Intermediate maple syrup urine disease... NM_183050.4:c.82_92GGCGCGGGGCT[1]HomozygousAutosomal, RecessiveTabbouche et al, 2014
248600.G.2SudanUnknown Elevated plasma branched chain amino aci... NM_000709.4:c.1227_1229delHomozygousAutosomal, RecessiveAl-Jasmi at al. 2016 UAE resident(s) of S...
248600.2.1United Arab EmiratesUnknown Maple syrup urine disease... NM_001918.4:c.1281+1G>THomozygousAutosomal, RecessiveAl-Shamsi et al. 2014
248600.7United Arab EmiratesUnknown Elevated plasma branched chain amino aci... NM_001918.4:c.1281+1G>THomozygousAutosomal, RecessiveAl-Jasmi at al. 2016
248600.G.3YemenUnknown Elevated plasma branched chain amino aci... NM_001918.4:c.634C>THomozygousAutosomal, RecessiveAl-Jasmi at al. 2016 UAE resident(s) of Y...

Other Reports

Bahrain

Mohammad and Ebrahim, 1985, described the first diagnosed cases of MSUD from Bahrain: two infants, born to consanguineous healthy Bahraini parents, both of whom succumbed to the disease. The authors opined that the late introduction of MSUD formula, lack of facilities for monitoring the amino acid levels, and the presence of skin infection contributed to their fatal outcome.

[Mohammad AM, Ebrahim AHK. Maple syrup urine disease in Bahrain. Bahrain Med Bull. 1985; 7(3):114-7.]

Al Arrayed et al, 1999, applied newborn screening to 1000 Bahraini newborns taken at random during two years. Preliminary results showed ten abnormal cases out of 1000 newborns (incidence 1%) although it was expected to find 100 affected births with metabolic diseases in every 1000 newborns annually. Maple syrup urine disease was commonly found among Bahraini infants. In 2006, Al-Arrayed indicated that MSUD occurs in Bahrain at an approximate incidence of 2/10,000 births.

[Al Arrayed SS, Al Jishi E, Abbasi A, Rashed MS, Ozand PT. Newborn screening by using mass spectrometry. Bahrain Med Bull. 1999; 21(4).]

Jordan

The Centre for Arab Genomic Studies Work Group (2006) conducted a retrospective study for metabolic disorders described at AlWasl Hospital in Dubai between 1997 and 2006. Only two cases of MSUD were observed in Jordanian (one male and one female) residents of the UAE.

Kuwait

Yadav and Reavey, 1988, presented a summary of the results of quantitative amino acid analysis in 800 subjects over a three-year period in Al-Sabah Hospital, Kuwait. Thirty-five patients with aminoacidopathy were identified, all but two of whom were the offspring of first-degree consanguineous marriages: nine cases of phenylketonuria, one benign hyperphenylalaninemia, seven non-ketotic hyperglycinemia, five tyrosinemia, five homocystinuria, four citrullinemia, two cystinuria, one hyperprolinemia, and one case of maple syrup urine disease were encountered.

Lebanon

In a retrospective analysis of IEMs diagnosed over a 12-year period (1998-2010) in a hospital in Lebanon, Karam et al. (2013) found 40 patients diagnosed with MSUD. The median age of diagnosis was 5-months.

Tabbouche et al, 2014, studied a Lebanese patient with Maple Syrup Urine Disease and found a gross microdeletion in the BCKDHA gene. The deletion, from exon 5 to exon 8, was predicted to result in a frameshift, premature termination and complete loss of function of the protein. 

Oman

Joshi et al, 2002, carried out a retrospective analysis of all patients born with inborn errors of metabolism in Oman between 1998 and 2000. Among the 82 patients, one was diagnosed with MSUD [CTGA Database Editor's note: Computed annual incidence rate is 0.8/100,000]. A few years later, Joshi and Venugopalan (2007) conducted a study over a seven year period (1998-2005) to evaluate the clinical profiles of 166 neonates at high risk of having inborn errors of metabolism. Of these, ten babies (four males, six females) were diagnosed with maple syrup urine disorder. 

Al-Riyami et al, 2012, reported on the types and patterns of IEMs encountered in a sample of 1100 high-risk neonates referred to SQU Hospital in Oman over a 10-year period (1998-2002). A total of 119 of these neonates were found to test positive for an IEM. MSUD was detected in 17 neonates (10 females, 7 males), belonging to 13 families. 

Qatar

In 2003, the Hamad Medical Corporation, in partnership with the University Children's Hospital of Heidelberg, built a comprehensive newborn screening program. Between December 2003 and July 2006, Lindner et al, 2007, investigated 25,214 neonates born in Qatar for inborn errors of metabolism and endocrine disorders. Two neonates were diagnosed with MSUD.

Saudi Arabia

Subramanyam et al, 1990, measured plasma amino acid concentrations in infants with maple syrup urine disease using reversed phase high performance liquid chromatography (HPLC). During a period of three years nearly 14 cases of MSUD were observed; suggesting an alarmingly high rate of incidence of the disease in the Kingdom as compared to the West.

Brismar et al, 1990, reviewed the cases of 10 infants with classical maple syrup urine disease (MSUD) and two with variant MSUD using a total of 26 CT scans and 13 MR examinations of the brain during different stages of their disease. 

Al Awamy and Al-Madan, 2002, described the first cases of an acrodermatitis enteropathica-like rash in isoleucin deficient patients with maple syrup urine disease in the country. The first case was that of an 8-day old female, born to consanguineous parents, who presented with poor feeding, vomiting and convulsions. Despite treatment, the patient died of a cardiopulmonary arrest. The second case was that of a six-month old infant who was evaluated for a skin rash. Like the first patient, he too went into cardiopulmonary arrest and died. 

[Al Awamy BH, Al-Madan MS. Cutaneous lesions during dietetic therapy in patients with maple syrup urine disease. Kuwait Med J. 2002; 34(3):224-6.]

Moammar et al, 2010, reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Aminoacidopathies were diagnosed in 38 out of 248 cases (16%). Among them, twelve cases from seven families were found to have MSUD. Only one case of MUSD was confirmed enzymatically. The estimated incidence of this condition is 7 in 100,000 live births.

United Arab Emirates

[See: Jordan > CAGS Work Group, 2006].

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