Non-immune hydrops fetalis (NIHF) can be one of the earliest signs of MPS VII1,2

MPS VII often goes undiagnosed in fetal-stage infants with idiopathic NIHF3

Hydrops fetalis is a life-threatening fetal state that is characterized by increased fluid accumulation in fetal soft tissues and body cavities. It can be diagnosed in utero or postnatally.3

Specifically, non-immune hydrops fetalis3

  • Accounts for ~90% of cases of hydrops, with an incidence of 1 in 1700 to 3000 pregnancies, and has many causes.
  • Has been reported as idiopathic in older studies, but recent larger studies and a systematic review report that a cause can be found in up to 85% of cases.

About 70% of the time, NIHF clinical workups did not test for lysosomal storage disorders (LSDs) like MPS VII.3

The NIHF and MPS VII correlation has historically been under recognized1,3

  • MPS VII is the most commonly diagnosed LSD in cases of NIHF 3
  • ~40% of MPS VII patients have a history of NIHF, from a survey of 118 patients in 25 countries 1

Matthew’s story

Matthew, born prematurely at 34 weeks with multiple health concerns, was found by doctors to have non-immune hydrops fetalis (NIHF). At 18 months of age, he became one of the very few children to be diagnosed with both NIHF and MPS VII.

Despite challenges, he has learned sign language and is eager to learn more. A popular child at the rehabilitation facility where he lives, his smile and happy demeanor have left an imprint on all who care for him. Matthew’s strength and fighting spirit continue to inspire us all.

A literature analysis reporting cases of NIHF from 1979 to 2014 was performed to3

  • Evaluate the significance of LSDs as an underlying etiology of NIHF
  • Determine whether identifying LSDs would be clinically useful in the workup of NIHF

Of the 678 total NIHF cases identified

  • 5.2% (35) were diagnosed with LSD.
  • 70.3% (477) had a diagnosis other than LSD.
  • 24.5% (166) were idiopathic.

Most common diagnosed LSDs in 35 cases3

Mucopoly­saccharidosis type VIIβ-glucuronidase7 (20.0)
Gaucher diseaseGlucocerebrosidase6 (17.1)
GM1-gangliosidosisβ-galactosidase5 (14.3)
SialidosisSialidase4 (11.4)
Mucopoly­saccharidosis type not specifiedNot applicable4 (11.4)
Niemann-Pick disease type CNPC1, NPC23 (8.5)
GalactosialidosisProtective protein cathepsin A2 (5.7)
Infantile sialic acid storage diseaseTransport protein1 (2.9)
Niemann-Pick A diseaseSphingomyelinase1 (2.9)
Mucopoly­saccharidosis type IVaN-acetylgalactosamine-6-sulfatase1 (2.9)
Mucolipidosis IIUDP-N-Ac-glycosaminyl phosphotransferase1 (2.9)

LSD, lysosomal storage disorder.
aLSDs with 0 cases (0%) are not shown in this table and do not count towards total of 35 cases.

Importance of comprehensive testing3

LSDs have been reported to account for about 1-15% of the causes of NIHF cases. Yet in clinical practice, these LSDs are often not evaluated.

A literature analysis found that of the 18-30% of cases in which the initial NIHF workup did not reveal a probable etiology

  • Testing for LSDs resulted in a diagnosis in 17.4% of cases.
  • Evidence supports an estimate that 29.6% of those cases that would have been classified as idiopathic would have had a diagnosis of LSD.
  • The more common positive LSDs were mucopolyaccharidosis type VII, Gaucher disease, and GM1-gangliosidosis.

Based on the literature analysis, a 2-step approach is recommended for identifying LSDs as a cause of NIHF:3

Common causes of NIHF should be evaluated
For cases that remain idiopathic after the initial NIHF workup, comprehensive testing for LSDs should be done

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References: 1. Montaño AM, Lock-Hock N, Steiner RD, et al. Clinical course of sly syndrome (mucopolysaccharidosis type VII). J Med Genet. 2016;53(6):403-418. 2. National MPS Society. A Guide to Understanding MPS. Durham, NC: National MPS Society. Accessed August 14, 2018. 3. Gimovsky AC, Luzi P, Berghella V. Lysosomal storage disease as an etiology of nonimmune hydrops. Am J Obstet Gynecol. 2015;212(3):281-290.