This page is part of the MII Implementation Guide Seltene Erkrankungen (v2027.0.0-ballot: 2027 Ballot 1) based on FHIR (HL7® FHIR® Standard) R4. This is the current published version in its permanent home (it will always be available at this URL). For a full list of available versions, see the Directory of published versions

Case Example Spinal Muscular Atrophy (SMA)

Overview

This document contains the semantic annotations for a case example of spinal muscular atrophy (SMA) in a newborn.

Timeline

1. Newborn screening (2024-07-18)

• Suspected diagnosis: spinal muscular atrophy (SMA)
• Setting: screening
• Status: suspected

2. Outpatient first presentation (2024-07-22)

• Admission diagnosis:
  • ICD-10-GM: G12.0 "Infantile spinal muscular atrophy type 1"
  • Orpha: 83330
• Setting: outpatient
• Center: specialized SMA center

3. Molecular genetic diagnostics (2024-07-26)

• Specimen: EDTA blood
• Findings:
  • SMN1 gene: 0 copies (pathological)
  • SMN2 gene: 2 copies
• Interpretation: disease-causing
• Confirmation: clinical suspicion confirmed

4. Inpatient therapy (2024-07-29)

• Treatment: gene therapeutic
• Concomitant medication: prednisolone (pre-therapeutic)
• Procedure code: 6-00d.0
• Complications: none
• Post-therapeutic laboratory values:
  • ALT: normal
  • AST: normal
  • Platelet count: normal

5. Follow-up (2024-08-12)

• Setting: outpatient
• Laboratory values:
  • ALT: normal
  • AST: normal
  • Platelet count: normal
  • Troponin T hs: 106 ng/l (elevated)
• Troponin course (pre-therapeutic):
  • 2024-07-22: 92 ng/l
  • 2024-07-28: 58 ng/l
  • 2024-08-01: 57 ng/l
  • 2024-08-12: 106 ng/l

Semantic annotations

Patient

• Sex: female
• Date of birth: ~July 2024 (newborn)
• Relevant characteristics: newborn with SMA

Family history

• Great-grandmother: unknown muscle disease
• Rest of family: unremarkable

Diagnoses

1. Main diagnosis:
   • Name: infantile spinal muscular atrophy type 1
   • ICD-10-GM: G12.0
   • Orpha: 83330
   • SNOMED CT: 80854005 (Werdnig-Hoffmann disease)
   • Status: confirmed by molecular genetics
   • Onset: neonatal

Genetic findings

1. SMN1 gene deletion:
   • Gene: SMN1 (OMIM: 600354, HGNC: HGNC:11117)
   • Variant: homozygous deletion
   • Copy number: 0
   • Interpretation: pathological, disease-causing
2. SMN2 gene copy number:
   • Gene: SMN2 (OMIM: 601627, HGNC: HGNC:11118)
   • Copy number: 2
   • Interpretation: phenotype modifier

Procedures

1. Gene therapy:
   • OPS code: 6-00d.0
   • SNOMED CT: 788110002 (Gene therapy)
   • Date: 2024-07-29
   • Drug: onasemnogene abeparvovec (Zolgensma)
   • UNII: MLU3LU3EVV
   • Concomitant medication: prednisolone

Laboratory values

1. ALT (alanine aminotransferase):
   • LOINC: 1742-6
   • Status: normal (post-therapeutic)
2. AST (aspartate aminotransferase):
   • LOINC: 1920-8
   • Status: normal (post-therapeutic)
3. Platelet count:
   • LOINC: 777-3
   • Status: normal (post-therapeutic)
4. Troponin T hs:
   • LOINC: 6598-7
   • Values: elevated pre-therapeutically, rising over time
   • Unit: ng/l

Treatment plan

• Gene therapy: administered once
• Prednisolone: continued after discharge
• Follow-up:
  • Pediatric care
  • Human genetic counseling
  • Social-pediatric center
  • Center-based follow-up

FHIR mapping

Profiles used

The list below states what the example instances actually declare in meta.profile. Resources without an entry deliberately use the plain FHIR base resource: this module profiles what is specific to rare diseases and points at the neighbouring MII modules for the rest — laboratory values belong to Laborbefund, variant findings to Molekulargenetischer Befund. Neither is a dependency of this module, and nothing here inherits from them.

• Clinical diagnosis (suspected, clinical): mii-pr-seltene-clinical-diagnosis
• Genetic diagnosis (confirmed, excluded): mii-pr-seltene-genetic-diagnosis
• Therapy recommendation, medicinal (gene therapy): mii-pr-seltene-therapieempfehlung
• Therapy recommendation, non-medicinal (physiotherapy): mii-pr-seltene-therapieempfehlung-nicht-medikamentoes
• Therapy performed (NARSE): mii-pr-seltene-therapie-durchgefuehrt
• Unprofiled base resources: Patient, the laboratory and variant Observations, the MolGen DiagnosticReports, and the transaction Bundle

Resource overview

Patient and family history

Resource ID	Type	Description	Date	Status/details
mii-exa-seltene-patient-sma-001	Patient	Newborn girl	Birth: ~2024-07-01	ID: SMA-2024-001
mii-exa-seltene-family-history-001	FamilyMemberHistory	Great-grandmother with muscle disease	2024-07-22	Relation: uncertain

Diagnosis course

Resource ID	Type	Description	Date of determination	Verification status	Codes
mii-exa-seltene-condition-sma-suspected	Condition	Suspected SMA	2024-07-18	unconfirmed	SNOMED: 80854005
mii-exa-seltene-condition-sma-clinical	Condition	Clinical diagnosis SMA type 1	2024-07-22	provisional	ICD-10: G12.0, Orpha: 83330
mii-exa-seltene-condition-sma-genetic	Condition	Confirmed SMA type 1	2024-07-26	confirmed	ICD-10: G12.0, Orpha: 83330

Screening and genetic findings

Resource ID	Type	Test/gene	Finding	Date	Interpretation
mii-exa-seltene-observation-sma-screening	Observation	SMA newborn screening (LOINC: 92005-8)	SMN1 exon 7 not detectable	2024-07-18	Positive for SMA
mii-exa-seltene-variant-smn1-001	Observation	SMN1 (HGNC:11117) — confirmatory	0 copies (deletion)	2024-07-26	Pathological, disease-causing
mii-exa-seltene-variant-smn2-001	Observation	SMN2 (HGNC:11118) — confirmatory	2 copies	2024-07-26	Phenotype modifier

Treatment

Resource ID	Type	Description	Date	Code	Details
mii-exa-seltene-procedure-gentherapy-001	Procedure	Gene therapy (onasemnogene abeparvovec)	2024-07-29	OPS: 6-00d.0, UNII: MLU3LU3EVV	With prednisolone, without complications

Laboratory values

Resource ID	Type	Parameter	Date	Value	Interpretation
mii-exa-seltene-observation-troponin-001	Observation	Troponin T hs	2024-07-22	92 ng/l	Elevated
mii-exa-seltene-observation-troponin-002	Observation	Troponin T hs	2024-07-28	58 ng/l	Elevated
mii-exa-seltene-observation-troponin-003	Observation	Troponin T hs	2024-08-01	57 ng/l	Elevated
mii-exa-seltene-observation-troponin-004	Observation	Troponin T hs	2024-08-12	106 ng/l	Elevated
mii-exa-seltene-observation-alt-001	Observation	ALT	2024-07-29	-	Normal
mii-exa-seltene-observation-ast-001	Observation	AST	2024-07-29	-	Normal
mii-exa-seltene-observation-plt-001	Observation	Platelet count	2024-07-29	-	Normal

Encounters

Resource ID	Type	Description	Date	Setting	Linked diagnosis
mii-exa-seltene-encounter-screening-001	Encounter	Newborn screening	2024-07-18	Screening	mii-exa-seltene-condition-sma-suspected
mii-exa-seltene-encounter-ambulant-001	Encounter	First presentation SMA center	2024-07-22	Outpatient	mii-exa-seltene-condition-sma-clinical
mii-exa-seltene-encounter-stationaer-001	Encounter	Inpatient gene therapy	2024-07-29/30	Inpatient	mii-exa-seltene-condition-sma-genetic
mii-exa-seltene-encounter-nachsorge-001	Encounter	Follow-up	2024-08-12	Outpatient	mii-exa-seltene-condition-sma-genetic

Clinical assessments

Resource ID	Type	Description	Date	Encounter	Key findings
mii-exa-seltene-clinical-impression-erstvorstellung	ClinicalImpression	Initial clinical assessment	2024-07-22	mii-exa-seltene-encounter-ambulant-001	Family history, troponin ↑, suspected SMA type 1
mii-exa-seltene-clinical-impression-nachsorge	ClinicalImpression	Follow-up assessment after gene therapy	2024-08-12	mii-exa-seltene-encounter-nachsorge-001	Troponin still ↑ (pre-existing), ALT/AST/PLT normal

Bundle

Resource ID	Type	Description	Number of entries
mii-exa-seltene-bundle-sma-complete	Bundle	Transaction bundle with all resources	22 resources

Resource diagrams

Overall view of all resources and their relationships

Timeline

Implementation

The complete FHIR resources are defined in the FSH sources of this module (input/fsh/Beispiel_SMA/), including the transaction bundle.